Pre-emptive, early, and delayed alendronate treatment in a rat model of knee osteoarthritis: effect on subchondral trabecular bone microarchitecture and cartilage degradation of the tibia, bone/cartilage turnover, and joint discomfort
Pre-emptive, early, and delayed alendronate treatment in a rat model of knee osteoarthritis: effect on subchondral trabecular bone microarchitecture and cartilage degradation of the tibia, bone/cartilage turnover, and joint discomfort
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DOI：
10.1016/j.joca.2013.06.020
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发表时间：
2013-10-01
影响因子：
7
通讯作者：
Kuliwaba, J. S.
中科院分区：
文献类型：
--
作者：
Mohan, G.;Perilli, E.;Kuliwaba, J. S.
目的：双膦酸盐被认为是潜在的改善骨关节炎（OA）的药物。本研究调查了预先、早期和延迟阿仑膦酸钠（ALN）治疗对低剂量碘乙酸（MIA）诱导的大鼠膝关节OA的软骨下骨小梁和软骨的疗效。雄性大鼠预先接受（n = 12，第0天-第2周末）、早期（n = 12，第2周末-第6周末）或延迟（n = 12，第6周末-第10周末）ALN治疗（30 μ g/kg/周）。在2周后使用体内微型计算机断层扫描（micro-CT）扫描预先接受AlN治疗的大鼠，然后处死，在2周和6周后扫描早期接受AlN治疗的大鼠并处死，并且在OA诱导后2、6和10周扫描延迟接受AlN治疗的大鼠并处死。处死后，进行胫骨的骨组织形态计量学和组织学以及生物标志物分析。结果：MIA诱导的软骨和软骨下骨的病理改变与人类进行性OA相似。预先ALN治疗保留了软骨下松质骨微结构，防止了骨丢失，降低了骨转换和关节不适。预先ALN治疗对软骨降解有中度影响。早期和延迟ALN治疗防止损失的骨小梁和骨转换率下降，但没有显着的影响软骨degradation.Conclusion：ALN防止增加骨转换率，并保留在实验性OA的软骨下骨的结构完整性。治疗开始的时间点对于治疗OA至关重要。在OA中同时治疗软骨下骨和软骨将在临床上更有益。(C)2013年国际骨关节炎研究学会。由爱思唯尔有限公司出版。保留所有权利。
Objective: Bisphosphonates are considered potential disease modifying osteoarthritis (OA) agents. The present study investigated the efficacy of pre-emptive, early, and delayed alendronate (ALN) treatment initiation on subchondral trabecular bone and cartilage in low-dose monosodium iodoacetate (MIA)-induced knee OA in rats.Methods: Male rats received pre-emptive (n = 12, day 0-end of week 2), early (n = 12, end of week 2-end of week 6), or delayed (n = 12, end of week 6-end of week 10) ALN treatment (30 mu g/kg/week). Pre-emptive ALN-treated rats were scanned using in vivo micro-computed tomography (micro-CT) after 2 weeks and then sacrificed, early ALN-treated rats were scanned after 2 and 6 weeks and sacrificed, and the delayed ALN-treated rats were scanned after 2, 6, and 10 weeks of OA induction and sacrificed. After sacrifice, bone histomorphometry and histology of the tibia and biomarker analyses were undertaken. Changes in hind limb weight-bearing were assessed from day -1 until day 14.Results: MIA-induced pathological features similar to progressive human OA in the cartilage and subchondral bone. Pre-emptive ALN treatment preserved subchondral trabecular bone microarchitecture, prevented bone loss, decreased bone turnover and joint discomfort. Pre-emptive ALN treatment had moderate effects on cartilage degradation. Early and delayed ALN treatments prevented loss of trabeculae and decreased bone turnover, but had no significant effect on cartilage degradation.Conclusion: ALN prevented increased bone turnover and preserved the structural integrity of subchondral bone in experimental OA. The time point of treatment initiation is crucial for treating OA. Treating both the subchondral bone and cartilage in OA would be clinically more beneficial. (C) 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.